Exercise Reduces Tumor Growth And Burden In A Mouse Model Of Non-small Cell Lung Cancer

Abstract

INTRODUCTION: Exercise has been shown to reduce the prevalence of certain cancers. Moderate-intensity exercise has been shown to have significant effects on tumor initiating mechanisms in mice resulting in decreased tumor incidence for a variety of cancers including pancreatic, gastrointestinal, and mammary. This is the first report of the role that exercise plays in the suppression of spontaneous murine lung cancer. METHODS: CCSPCre/LSL-KrasG12D mice were generated by crossing a mouse with the LSL-K-rasG12D mutant allele with a mouse harboring Cre recombinase inserted in the Clara cell secretory protein (CCSP) locus. Tumor-bearing progeny were assigned to either exercise (EX) or sedentary control groups. At tumor onset (4wks of age), 10wks of moderate exercise training was conducted for the EX group on a motor-driven treadmill (13.5m/min) for 45min/day, 5days/wk. Tumor burden was assessed by two variables: (1) visual count of lung surface tumor numbers; and (2) internal tumor volume established from H&E stains. Homogenized spleen samples were analyzed via ELISA for IL-6 and TNF-α protein levels. RESULTS: For sedentary mice (N=14) lung tumor count was 40.57 ± 3.483 tumors (mean ± SEM). Lung tumor count in the exercised mice (N=10) was significantly reduced to 21.80 ± 1.705 tumors (p<0.001). Sedentary mice (N=6) tumor percentage of lung volume was 12.34 ± 0.528%. Percent lung tumor volume in exercised mice (N = 8) was significantly reduced to 6.913 ± 0.262% resulting in a 44% reduction of tumors within lung tissue. IL-6 and TNF-alpha spleen data did not show any significant changes due to exercise in relation to lung cancer. CONCLUSIONS: These results demonstrate that moderate exercise can slow the progression of tumorigenesis in a mouse model of lung cancer. However, the exercise mechanism of action remains unclear; while we did see a trend toward decreased levels of IL-6, no significant changes were seen in systemic pro-inflammatory cytokines IL-6 and TNF-alpha. Lung cancer is the leading cause of cancer mortality worldwide with current treatments resulting in an average 17% five year survival rate. Moderate exercise may be a practical method for patients to help suppress tumor progression.